In the Belgian phase II CHEERS trial reported in JAMA Oncology, Spaas et al evaluated the addition of stereotactic body radiotherapy (SBRT) to anti–PD-1/PD-L1 immune checkpoint inhibitor therapy, with SBRT directed to a maximum of three lesions, in patients with advanced solid tumors. The investigators found that such treatment was safe, but it did not improve progression-free or overall survival outcomes.
Study Details
The open-label multicenter trial included 96 evaluable patients with locally advanced or metastatic melanoma, renal cell carcinoma, urothelial carcinoma, head and neck squamous cell carcinoma, or non–small cell lung carcinoma. Patients were randomly assigned between March 2018 and October 2020 to immune checkpoint inhibitor treatment (nivolumab, pembrolizumab, or atezolizumab at physician discretion) with (n = 45) or without (n = 51) SBRT at 8 Gy in 3 fractions every other day to a maximum of three lesions prior to the second or third immune checkpoint inhibitor cycle.
In total, 75% of patients had more than three metastatic lesions and 68% had received at least one prior line of systemic therapy. The primary endpoint was progression-free survival in the intention-to-treat population.
Key Findings
Median follow-up was 12.5 months (range = 0.7–46.2 months). Seven patients in the SBRT plus immune checkpoint inhibitor group did not complete the radiotherapy course due to early disease progression or intercurrent illness.
Median progression-free survival was 4.4 months (95% confidence interval [CI] = 2.8–7.8 months) in the SBRT plus immune checkpoint inhibitor group vs 2.8 months (95% CI = 2.5–8.4 months) in the immune checkpoint inhibitor group (hazard ratio [HR] = 0.95, 95% CI = 0.58–1.53, P = .82); no differences were observed according to disease burden or tumor type.
Median overall survival was 14.3 months (95% CI = 11.0 months to not reached) in the SBRT plus immune checkpoint inhibitor group vs 11.0 months (95% CI = 9.0 months to not reached) in the immune checkpoint inhibitor group (HR = 0.82, 95% CI = 0.48–1.41, P = .47). No differences were observed according to disease burden or tumor type.
Objective response was observed in 27% vs 22% of patients (P = .56); a local control rate of 75% was observed in patients receiving radiotherapy.
Acute treatment-related toxicity of any grade and grade ≥ 3 occurred in 78% and 18% of patients in the SBRT plus immune checkpoint inhibitor group, respectively, vs 79% and 18% of the immune checkpoint inhibitor group. No treatment-related deaths were reported.
The investigators concluded, “This phase II randomized clinical trial demonstrated that while safe, adding subablative stereotactic radiotherapy of a limited number of metastatic lesions to immune checkpoint inhibitor monotherapy failed to show improvement in progression-free or overall survival.”
Mathieu Spaas, MD, of the Department of Radiation Oncology, Ghent University Hospital, Ghent University, is the corresponding author for the JAMA Oncology article.
Disclosure: The study was supported by Kom Op Tegen Kanker and Varian Medical Systems. For full disclosures of the study authors, visit jamanetwork.com.
